Pediatric autoimmune Parkinsonism and response to deep brain stimulation.

INTRODUCTION: Influenza virus has been associated with cases of Parkinsonism, yet a direct relationship has not been confirmed in the literature. Different mechanisms of post-infectious Parkinsonism have been proposed including inflammatory, oxidative stress, and autoimmune. We report a first to our knowledge case of pediatric autoimmune Parkinsonism with autoantibodies to dopamine D2L receptor (anti-DRD2L antibodies), who underwent deep brain stimulation (DBS) of bilateral globus pallidi (GPi). CASE REPORT: A 13-year-old girl presented with Parkinsonism features after a severe case of influenza A. She underwent extensive work-up and was found to have elevated titers for anti-DRD2L antibodies. Patient was initially treated with IVIG and plasmapheresis with mild improvement, but her condition continued to worsen. She was responsive to levodopa; however, she developed severe dyskinesia. Patient underwent DBS implantation resulting in partial improvement in bradykinesia, tremors, and dyskinesia. CONCLUSION: This case is meant to raise awareness of a rare potential autoimmune complication after influenza virus and to share the experience and outcome using DBS to palliate some of the symptoms.

Pro-inflammatory dopamine-2 receptor-specific T cells in paediatric movement and psychiatric disorders.

OBJECTIVES: A dysregulated inflammatory response against the dopamine-2 receptor (D2R) has been implicated in movement and psychiatric disorders. D2R antibodies were previously reported in a subset of these patients; however, the role of T cells in these disorders remains unknown. Our objective was to identify and characterise pro-inflammatory D2R-specific T cells in movement and psychiatric disorders. METHODS: Blood from paediatric patients with movement and psychiatric disorders of suspected autoimmune and neurodevelopmental aetiology (n = 24) and controls (n = 16) was cultured in vitro with a human D2R peptide library, and D2R-specific T cells were identified by flow cytometric quantification of CD4+CD25+CD134+ T cells. Cytokine secretion was analysed using a cytometric bead array and ELISA. HLA genotypes were examined in D2R-specific T-cell-positive patients. D2R antibody seropositivity was determined using a flow cytometry live cell-based assay. RESULTS: Three immunodominant regions of D2R, amino acid (aa)121-131, aa171-181 and aa396-416, specifically activated CD4+ T cells in 8/24 patients. Peptides corresponding to these regions were predicted to bind with high affinity to the HLA of the eight positive patients and had also elicited the secretion of pro-inflammatory cytokines IL-2, IFN- γ, TNF, IL-6, IL-17A and IL-17F. All eight patients were seronegative for D2R antibodies. CONCLUSION: Autoreactive D2R-specific T cells and a pro-inflammatory Th1 and Th17 cytokine profile characterise a subset of paediatric patients with movement and psychiatric disorders, further underpinning the theory of immune dysregulation in these disorders. These findings offer new perspectives into the neuroinflammatory mechanisms of movement and psychiatric disorders and can influence patient diagnosis and treatment.